MYFLAI07: Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)

Sponsor

University Hospital, Udine, Italy (Other)

Overall Status

Completed

CT.gov ID

NCT00909168

Collaborator

(none)

130

Enrollment

Location

Arm

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, open, non-randomized, non-controlled, phase II, clinical trial for treatment of newly diagnosed AML patients, younger than 66 years.

Trial is based on:

INDUCTION: FLAI + Gemtuzumab-Ozogamicin (FLAI-GO).
CONSOLIDATION: Intermediate dose AraC + IDA (IDAC+IDA) +/- one course of high dose AraC (HDAC)
INTENSIFICATION: Allo-BMT, ASCT
MAINTENANCE: AraC

Primary endpoints:

Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin.
RFS, DFS and OS.

Secondary endpoints:

Evaluation of Minimal Residual Disease by WT1 (and other biologic markers) expression and monitoring.
Evaluation of prognostic clinical relevance of biological features at onset.
Feasibility and outcome of consolidation with BMT.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Efficacy of FLAIMy	Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg FLUDARABINE: 25 mg/m2/day, 250 FS in 30', start h 9 - 1, 2, 3, 4, 5 ARABINOSYL-CYTOSINE (Cytarabine): 2 g/m2/day, 500 FS in 3 h, start h 13 - 1, 2, 3, 4, 5 IDARUBICIN: 10 mg/m2/day, 100 FS in 1 h, start h 16 - 1, 3, 5 GEMTUZUMAB OZOGAMICIN (Mylotarg): 5 mg, single dose 500 FS in 4 h - 6

Arm

Intervention/Treatment

Experimental: Efficacy of FLAIMy

Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg

FLUDARABINE: 25 mg/m2/day, 250 FS in 30', start h 9 - 1, 2, 3, 4, 5 ARABINOSYL-CYTOSINE (Cytarabine): 2 g/m2/day, 500 FS in 3 h, start h 13 - 1, 2, 3, 4, 5 IDARUBICIN: 10 mg/m2/day, 100 FS in 1 h, start h 16 - 1, 3, 5 GEMTUZUMAB OZOGAMICIN (Mylotarg): 5 mg, single dose 500 FS in 4 h - 6

Outcome Measures

Primary Outcome Measures

Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin. [one year]
RFS, DFS and OS. [one year]

Secondary Outcome Measures

Evaluation of Minimal Residual Disease by WT1 (and other biologic markers) expression and monitoring. [one year]
Evaluation of prognostic clinical relevance of biological features at onset. [one year]
Feasibility and outcome of consolidation with BMT. [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-65 years.
WHO PS grade 0-2 (Appendix B) or Karnofsky > 70.
AML according to the new WHO criteria, i.e., % of BM blasts ≥ 20%. NB. this % should be assessed on a BM aspiration or on a BM biopsy
All FAB subtypes except M3.
CD33 positivity (> 20%). It is mandatory to perform an immunotyping of the BM blasts in particular the determination of CD33 positivity, which will be used as a inclusion factor.
Previously untreated (except ≤ 14 days of Hydroxyurea) primary or secondary AML (including AML after MDS).
Adequate renal and liver function, i.e., creatinine < 2 mg/dl and bilirubin, ALT/AST ≤ 3 times the upper limit of normal.
Written informed consent

Exclusion Criteria:

Blast crisis of chronic myeloid leukemia.
AML supervening after other myeloproliferative diseases.
AML de novo or secondary previously pretreated.
Concomitant malignant disease.
Active central nervous system (CNS) leukemia.
Active uncontrolled infection [NB severe systemic infection should be excluded].
Concomitant severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease.
Cardiac ejection fraction of 50% or less.
Severe pulmonary dysfunction (CTC grade 3-4).
Severe concomitant neurological or psychiatric disease.
History of alcohol abuse.
HIV positivity.
Pregnancy.
Man and woman not agreeing to the adequate contraceptive precautions during study period and for at last 24 months after stop of therapy.
Any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.